Polypyridiniums with Inherent Autophagy‐Inducing Activity for Atherosclerosis Treatment by Intracellularly Co‐Delivering Two Antioxidant Enzymes

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Abstract Atherosclerosis is a chronic inflammatory disease of the arterial intima and becoming leading cause morbidity mortality worldwide. There considerable evidence that defective autophagy overproduction reactive oxygen species (ROS) are closely involved in development progression atherosclerosis. Here, polymer developed with inherent autophagy‐inducing activity to treat atherosclerosis by co‐delivering antioxidant enzymes. The lead material P5c screened from library polypyridiniums shows robust efficacy cytosolic protein delivery, efficiently delivers superoxide dismutase (SOD) catalase (CAT) into macrophages down‐regulate intracellular ROS. Moreover, activates sufficiently inhibits foam cell formation. nanoparticle loaded both SOD CAT further coated neutrophil membranes an ApoE −/− mice model. treatment exhibits potent anti‐atherosclerosis effect via activating autophagy, decreasing infiltration senescent cells atherosclerotic plaques, regulating M2 polarization macrophages, restoring structure function splenic corpuscles. offers multifaceted approach combat atherosclerosis, addressing cellular dysfunction need for targeted delivery within affected cells.

Language: Английский

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ROS-Responsive Cationic Polymers with Intrinsic Anti-Inflammatory Activity for Intracellular Protein Delivery

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The intracellular delivery of protein drugs via nanocarriers offers significant potential for expanding their therapeutic applications. However, the unintended activation innate immune responses and inflammation triggered by carriers presents a major challenge, often compromising efficacy. Here, we present oligoethylenimine-thioketal (OEI-TK), reactive oxygen species-responsive cationic polymer with intrinsic anti-inflammatory properties, to overcome this challenge. OEI-TK self-assembles electrostatically bovine serum albumin (BSA) form stable nanoparticles (OTB NPs) excellent encapsulation efficiency. In vitro studies confirmed that OTB NPs retained OEI-TK's antioxidant enhanced biocompatibility, efficiently delivered BSA into cells. Furthermore, facilitated β-galactosidase while preserving its enzymatic activity, demonstrating functional transport. These findings highlight as promising platform dual benefits modulation delivery, holding synergistic treatment inflammation-related diseases.

Language: Английский

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Rational Engineering of Cytosolic Delivery Systems for Protein Therapeutics

Accounts of Materials Research, Journal Year: 2024, Volume and Issue: 5(10), P. 1194 - 1209

Published: Sept. 10, 2024

Language: Английский

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A Dynamic Deferoxamine Polymer with Exceptional Performance in Mitochondrial Iron Depletion and Cytosolic Protein Delivery

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Deferoxamine (DFO) is an FDA‐approved naturally occurring iron chelator commonly used to treat transfusion‐induced overload. The abundant and flexible hydroxamic acid groups in DFO enable exceptional binding capacity high protein via hydrogen bonding interactions. However, the applications of sequester intracellular deliver proteins inside cells are limited due poor membrane‐permeability. Herein, fabrication a dynamic polymer proposed achieve robust delivery efficient mitochondrial depletion. Specifically, grafted onto polycatechol scaffold catechol‐boronate chemistry. obtained shows capacity, formed complexes show resistance toward serum proteins. It effectively delivers various cargo into cytosol treated with maintained bioactivity. In addition, cells, released efficiently depletes iron, which significantly inhibits oxidative phosphorylation glycolysis. Remarkable synergistic cytotoxic effects achieved when loaded toxic This study provides general strategy for facile preparation bioactive delivery, designed can be promising carrier therapeutics cancer.

Language: Английский

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Oxidative Stress, Glutaredoxins, and Their Therapeutic Potential in Posterior Capsular Opacification

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1210 - 1210

Published: Oct. 8, 2024

Posterior capsular opacification (PCO) is the most common long-term complication of cataract surgery. Traditionally, pathogenesis PCO involves residual lens epithelial cells (LECs), which undergo transdifferentiation into a myofibroblast phenotype, hyperproliferation, matrix contraction, and deposition. This process driven by marked upregulation inflammatory growth factors post-surgery. Recently, research on role redox environments has gained considerable attention. LECs, are in direct contact with aqueous humour after surgery, subjected to oxidative stress due decreased levels reduced glutathione increased oxygen content compared outer fibre layer before In this review, we examine critical formation. We also focus glutaredoxins (Grxs), antioxidative enzymes produced via deglutathionylation, their protective against formation, therapeutic potential. Furthermore, discuss latest advancements therapy, particularly development advanced pharmacological agents, emphasise importance approaches anti-inflammatory antioxidant treatments management. conclusion, review highlights significant roles PCO, effects Grxs potential therapies treating PCO.

Language: Английский

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Nanocarriers for intracellular delivery of proteins in biomedical applications: strategies and recent advances

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 10, 2024

Protein drugs are of great importance in maintaining the normal functioning living organisms. Indeed, they have been instrumental combating tumors and genetic diseases for decades. Among these pharmaceutical agents, those that target intracellular components necessitate use therapeutic proteins to exert their effects within targeted cells. However, protein is limited by short half-life potential adverse physiological environment. The advent nanoparticles offers a promising avenue prolonging drugs. This achieved encapsulating proteins, thereby safeguarding biological activity ensuring precise delivery into nanomaterial-based drug system mitigates rapid hydrolysis unwarranted diffusion minimizing side circumventing limitations inherent traditional techniques like electroporation. review examines established systems, including based on polymers, liposomes, nanoparticles. We delve operational principles transport mechanisms nanocarriers, discussing various considerations essential designing cutting-edge platforms. Additionally, we investigate innovative designs applications cytosolic systems medical research clinical practice, particularly areas tumor treatment, gene editing fluorescence imaging. sheds light current restrictions anticipates future avenues, aiming foster continued advancement this field.

Language: Английский

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A Hydroxyquinoline Polymer with Excellent Amyloidosis Inhibition and Protein Delivery Ability to Combat Amyloid-β-Mediated Neurotoxicity

Nano Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

The accumulation of abnormal protein deposits known as amyloid-β (Aβ) plaques contributes to the development and progression Alzheimer's disease. Aggregated Aβ exacerbates oxidative stress by stimulating production reactive oxygen species (ROS) in a detrimental feedback loop. 8-Hydroxyquinoline (8-HQ) is recognized for its ability inhibit or reverse aggregation reduce neurotoxicity. Here, an 8-HQ-based polymer, DHQ, was developed combat Aβ-mediated neurotoxicity delivering antioxidant enzyme. DHQ efficiently delivers superoxide dismutase into targeted cells, thereby downregulating intracellular ROS level. Additionally, polymer effectively inhibits fibrillization three proteins involved fibrosis, β-lactoglobulin (BLG), insulin, Aβ1-40, at nanomolar concentrations. Cell culture models demonstrated that reduces levels induced Aβ1-40 aggregation, rescuing cell viability preventing apoptosis. Intracellular delivery SOD further enhanced maintain homeostasis. This offers multifaceted approach treating diseases associated with amyloidosis.

Language: Английский

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Zwitterionic polymers with high serum tolerance for intracellular protein delivery

Biomaterials Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Modification with benzenesulphonate on a phase-transition polymer can improve the protein delivery efficacy, reduce cytotoxicity and adsorption.

Language: Английский

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A Supramolecular Deferoxamine–Crisaborole Nanoparticle Targets Ferroptosis, Inflammation, and Oxidative Stress in the Treatment of Retinal Ischemia/Reperfusion Injury

Nano Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 13, 2024

Retinal ischemia-reperfusion (IR) injury is a major cause of vision loss worldwide, with ferroptosis, oxidative stress, and inflammation playing key roles in its pathogenesis. Currently, treatments targeting multiple aspects this condition are limited. This study introduces supramolecular nanoparticle combining the phosphodiesterase 4 (PDE4) inhibitor crisaborole ferroptosis deferoxamine to address these pathological processes. Crisaborole forms dynamic bond via benzoxaborole-catechol chemistry, creating an amphiphilic molecule that assembles into nanoparticles. Treatment nanoparticles enhances glutathione peroxidase (GPX4) levels, downregulates ferroptosis-related genes [Acyl-CoA synthetase long chain family member (

Language: Английский

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